Abstract
HIV-1 infection is characterized by generalized deregulation of the immune system, resulting in increased chronic immune activation. However, some individuals called HIV controllers (HICs) present spontaneous control of viral replication and have a more preserved immune system. Among HICs, discordant results have been observed regarding immune activation and the frequency of different T cell subsets, including Treg and Th17 cells. We evaluated T cell immune activation, differentiation and regulatory profiles in two groups of HICs—elite controllers (ECs) and viremic controllers (VCs)—and compared them to those of cART-treated individuals (cART) and HIV-1-negative (HIV-neg) individuals. ECs demonstrated similar levels of activated CD4+ and CD8+ T cells in comparison to HIV-neg, while cART and VCs showed elevated T cell activation. CD4+ T cell subset analyses showed differences only for transitional memory T cell frequency between the EC and HIV-neg groups. However, VC individuals showed higher frequencies of terminally differentiated, naïve, and stem cell memory T cells and lower frequencies of transitional memory and central memory T cells compared to the HIV-neg group. Among CD8+ T cell subsets, ECs presented higher frequencies of stem cell memory T cells, while VCs presented higher frequencies of terminally differentiated T cells compared to the HIV-neg group. HICs showed lower frequencies of total Treg cells compared to the HIV-neg and cART groups. ECs also presented higher frequencies of activated and a lower frequency of resting Treg cells than the HIV-neg and cART groups. Furthermore, we observed a high frequency of Th17 cells in ECs and high Th17/Treg ratios in both HIC groups. Our data showed that ECs had low levels of activated T cells and a high frequency of activated Treg and Th17 cells, which could restrict chronic immune activation and be indicative of a preserved mucosal response in these individuals.
Highlights
HIV-1 controllers (HICs) are a rare group of HIV-1-infected individuals able to spontaneously control viral replication in the absence of combined antiretroviral therapy
Higher frequencies of Treg cells correlate with high plasma viral load and progression to AIDS [19,20,21,22,23,24,25,26,27,28], while lower frequencies have been observed for HICs/ long-term nonprogressors (LTNPs) [32,33,34,35] and combined antiretroviral therapy (cART)-treated patients [25,26,28,35,36] and are associated with an increase in viral-specific CD8+ T cell response [37,38,39,40,41]
Twenty-seven HICs were selected from the Instituto Nacional de Infectologia Evandro Chagas/Fiocruz (INI-Fiocruz) HIV-1 cohort for this study and were classified into two groups: (1) Elite controllers (ECs) (n = 14) if the plasma viral load (VL) measurements were below the lower detection limit (LDL and
Summary
HIV-1 controllers (HICs) are a rare group of HIV-1-infected individuals able to spontaneously control viral replication in the absence of combined antiretroviral therapy (cART) These individuals are divided into two groups: Elite controllers (ECs), who are able to keep plasma viral loads below the detection limit of clinical assays (currently < 40 HIV-1 RNA copies/ml), and viremic controllers (VCs), who present plasma viral loads < 2,000 HIV-1 RNA copies/ml [1]. Higher frequencies of Treg cells are associated with a decrease in the systemic immune activation [28,35,42]
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